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BioWorld MedTech Perspectives

FDA's off-label dilemma

As is widely known, the FDA is facing a change in leadership and has inked a memorandum staking out the agency's current position on the off-label promotion problem. Despite the continued vetting of the problem by the agency, the memo comes across as little more than a reiteration of the FDA's long-held views on commercial speech. Indeed the memo contains some suggestions that seem beyond rational consideration, but may reflect a certain anxiety among the agency's legal staff.

Many drafts, little actual guidance
To recap, the Medical Information Working Group, a loosely organized effort to nudge the FDA off its historical position, had filed two citizen petitions – the first in 2011 and the second two years later – to request that the FDA clarify its views on communication regarding off-label uses of drugs and devices. Among other things, the MIWG petitioned the agency to examine some sort of safe harbor for manufacturer communication regarding off-label use, but the FDA failed to act before cases such as Caronia started to filter through the courts to the detriment of the agency's position.

The agency was forced by the 21st Century Cures Act to issue the draft guidance on communication with payers and formularies, so this was hardly any concession. The FDA has also posted a new draft guidance that serves more or less as a Q&A on the subject of medical product communications for on-label uses, which is no concession at all. All of this comes several years after a 2011 draft guidance for unsolicited requests for off-label information regarding medical products, and the 2014 revised draft guidance for distribution of medical and scientific materials regarding unapproved uses. All in all, the FDA's efforts in this area appear to have met with little success.

Defending the status quo
The January 2017 FDA memo on the off-label question goes through the expected laundry list of reasons for the agency's attempts to regulate commercial speech, along with justifications for same, such as protecting public health. The memo stated that regulations "motivate the development of scientific evidence," but acknowledges the importance of information about off-label use.

The agency then oddly claims that its authorities foster innovation by the granting of exclusivity, but subsequently acknowledges that this function originated in legislation such as the Hatch-Waxman Amendments. Without mentioning the Patent and Trademark Office at all, the FDA further takes credit for patent protection, and for promoting orphan product development, again without discussing any underlying legislation.

The paper goes on to discuss alternatives to the status quo on off-label promotion, including absurdities such as an outright ban on off-label use and the imposition of caps on the volume of off-label use of medical products. As anyone who has ever spent five minutes reading on the off-label issue, physicians are not at all regulated by the FDA, and thus their off-label prescriptions are entirely outside the FDA's jurisdiction, making the agency's expression of these two possible resolutions difficult to comprehend.

The list of alternatives grows no less surreal as it unwinds, such as applying a greater level of taxation for medical products when used off-label, as though this sort of thing is at all within the agency's statutory power. Thus, much of this document comes across as an exercise in confabulation, particularly given the current political composition of the House, the Senate and the Oval Office.

Context, context, context
It's important to remember the context of the FDA's latest memo on off-label communication. The agency is facing the prospect of a new commissioner drawn from the ranks of venture capitalists, certainly a less appealing prospect to many at the agency than Scott Gottlieb, who formerly served as one of the FDA's associate commissioners. Say what one will of Gottlieb, he at least has some experience at the agency, a fact which many stakeholders no doubt find essential.

Nonetheless, the opposition to Gottlieb in a Senate hearing is likely to be loud and unyielding. He said in an April 23, 2008, post at the blog for Health Affairs that those who hew to an inflexibly high bar regarding off-label promotion "are guilty of pursuing a rigid standard that does not take measure of the consequences" of that adherence. He stated further that the idea that product labels are "the only determinant for acceptable scientific speech loses sight of the fact that these labels are slow to incorporate important medical results about the effectiveness of medical products," pointing out that those labels "are not the sole basis for medical practice."

Jim O'Neill of Mithril Capital Management is said to be among the alternative candidates for the FDA job, and has been credited with arguing that the FDA should approve drugs based strictly on safety data, which seems to resonate with President Trump's threat to cut FDA regulations by as much as 80 percent. One might safely assume O'Neill's confirmation hearing would prove noisier than one for Gottlieb, but Trump may be looking at a longer list than has been made public as of this writing.

All things considered, the FDA off-label memo was inevitable in terms of timing, but conspicuous in terms of tenor. It may be too much to assert that there is a whiff of desperation about it, but the document cannot be removed from context, and it is that very context – not to mention the memo's tone – that suggest that the supporters of the status quo are very worried, indeed, that drastic change is on the way.